Occur when an antibody present in the plasma of a transfusion recipient reacts with transfused red blood cells.
May be an immediate reaction from an antibody in the plasma at the time of transfusion or may be a delayed reaction from an anamnestic response of lymphocytes that may produce antibody over 7-14 days with a delayed hemolytic transfusion reaction.
The incidence of delayed hemolytic transfusion reactions is estimated to range from one in 500 transfusions to one in 10,000 transfusions.
Deaths are rare and are a result of transfusion of ABO incompatible blood, particularly group A or B units given to group O recipients.
Deaths are rare and are a result of transfusion of ABO incompatible blood, particularly group A or B units given to group O recipients.
In the past hemolysis was the most commonly cited cause of transfusion-associated deaths, but is now one of the least common fatal complications of transfusion,estimated risk of one death per 1,972, 000 red blood cell units transfused.
Deaths from hemolysis have been documented in emergency transfusions in patients with an unknown antibody history.
Hemolytic transfusion reactions in emergency transfusion situations where the blood has not been crossmatched is estimated at one reaction per 2000 transfusions.
Most fatal reactions are due to patient identification errors rather than to blood typing errors.
Signs include fever, chills, chest pain, hypotension nausea, flushing, dyspnea, and hemoglobinuria.
Associated with low haptoglobin levels, positive antiglobulin test, increased indirect bilirubin levels and hemoglobin in the plasma and or urine.
Delayed hemolytic transfusion reactions rarely cause more than transient clinical problems, but there are particular populations in which this is not true.
Patients at particular risk for delayed hemolytic transfusion reactions are those with frequent transfusion requirements, limited capacity to produce RBCs, or chronic hemolysis.
Sickle cell patients are at increased risk.
The incidence of delayed hemolytic transfusion reactions and hyper hemolysis range from 1-20% of transfusions.
Delayed hemolytic transfusion reactions account for 4.3% of all transfusion reactions and 16% of all serious reactions.
Immunologic incompatibility between a donor and recipient red blood cell types is the most common cause of clinically significant hemolytic transfusion reactions.
Incompatible A and B blood group antigens interact with pre-existing IgM antibodies and less commonly with hemolytic IgG antibodies, both of which fix and activate complement.
Formation membrane attack complexes consisting of C5 through C9 create multiple pores in the transfused red blood cell membrane, and initiates intravascular lysis.
Subsequently, excess cell free hemoglobin overwhelms the binding capacity of plasma albumin, haptoglobin, and hemopexin and can be measured with assays of hemoglobinemia and hemoglobinuria.
Free hemeb can induce renal vasoconstriction through nitric oxide scavenging.
Acute tubular necrosis and renal failure may occur.
Acute reactions, occurring within 24 hours of the transfusion, develop in response to red blood cell transfused in patients with pre-existing antibodies.
Naturally occurring antibody reactions against ABO-incompatible transfusions are implicated in the majority of fatal cases.
Incomplete complement activation creates the anaphylatoxins C3a and C5a, which activate mast cells, releasing histamine and serotonin.
Mast cells, along with hemolytic products, including red cell stromal components, activates monocytes and leukocytes, enzymes and anaphylatoxins mediate the release of pro inflammatory cytokines and chemokines.
Complement activation also activates the bradykinin and kallikrein systems and coagulation pathways resulting in the systemic inflammatory response syndrome of increased capillary permeability, vasodilatation, hypotension, fever, and disseminated intravascular coagulation.
In extreme cases the syndrome progresses to shock with multi organ failure and death.
incomplete complement activation also destroys incompatible red blood cells through C3B opsonization and monocyte/macrophage induced erythrophagocytosis in the liver and spleen.
Red blood cells coded with compliment to a faggot ties with gradual removal of the red cell membrane and surface area resulted in spherocytes and microspherocytes.
The extravascular destruction that occurs is associated with minimal release of free hemoglobin in the plasma.
Delayed hemolytic transfusion reactions, unlike acute hemolytic transfusion reactions, are caused by secondary immune responses in patients immunized by previous transfusions, allogeneic stem cell transplant or pregnancies.
Clinical reactions to delayed hemolytic transfusion reactions rarely occur, but may be associated with the anemia and jaundice.
On occasion severe hemolytic reactions occur in patients receiving long-term transfusions: sickle cell anemia, thalassemia.
Malaria can precipitate bystander hemolysis.
Immune related hemolysis may also occur after infusion of hematopoetic cells for transplantation or after solid organ transplantation where there is incompatibility between the donor’s plasma and the recipient’s red cells, termed minor ABO incompatibility, with red blood cell destruction in the recipient, and is the most common cause of clinically significant hemolysis in such cases.
Viable donor the lymphocytes (passenger lymphocytes) transferred with graft and produce isohemagglutinin that target recipient cells.
Life-threatening hemolysis due to passenger lymphocytes syndrome is reported to develop in 5 to 14 days after heart, lungs, liver, kidney, intestinal as well as hematopoietic stem cell infusions.
Hemolysis may be seen in patients treated with high-dose intravenous immune globulin, particularly in patients with blood group A or AB: higher group A antigens than f group B antigens on the red cells surface and the generally higher anti-A antibody titers in intravenous immunoglobulin products.
Non-immune mechanisms of hemolysis also occur and include transfusion of blood concurrently with hypoosmolar solutions, transfusion of overheated blood, transfusion of accidentally frozen blood, transfusion and depression through small bore needles or with the use of leukocyte reduction filters during processing may result in mechanical lysis of red cells.
Transfusion of blood contaminated with hemolytic bacteria can cause hemolysis.
Transfusion in patients with sepsis may precipitate hemolysis with transfusion of cells from patients with G6PD for other red cell defects.
Acute hemolytic transfusion reactions are considered a medical emergency and fever, flank pain, and reddish urine represent classic triad of acute hemolysis.
Symptoms appear within minutes to 24 hours after transfusion, is associated with a temperature increase of 1°C or more, chills, rigors, respiratory distress, anxiety, pain at the infusion site, flank or back pain, hypotension, or oliguria.
The severity of acute hemolytic transfusion reactions may be related to the titer strength of the anti-A and/or anti-B antibodies, in the recipients plasma, as well as the volume of incompatible blood transfusions and the rate of transfusion.
Most deaths associated with transfusions occur with 200 mL or more of incompatible blood, although volumes as small as 25 mL have been fatal, particularly in children.
If a suspected of an acute hemolytic transfusion reaction, the transfusion should be stopped immediately and blood saved for analysis for compatibility.
Visual inspection of urine and plasma, as well as for testing the urine and plasma free hemoglobin is undertaken.
Gram staining and cultures of the remaining transfused component are evaluated for infectious causes.
The findings of a positive direct anti-globulin test, which detects IgG or complement bound to the red cell membrane is pathognomonic of immune mediated hemolysis.
Conversely, the indirect anti-globulin test, or the indirect Coombs test, detects the presence of antibodies in the patients serum.
Delayed hemolysis that occurs days to a month after transfusion may occur, that is less evident than an acute reaction.
The temporal relationship is often overlooked in the presence of new onset anemia, jaundice, elevated LDH and bilirubin levels, decreased haptoglobin level in a patient with a prior transfusion or is a transplant recipient, or the likelihood of preformed but often evanescent antibodies due to pregnancy should suggest evaluation for a delayed hemolytic transfusion reaction.
With a delayed hemolytic transfusion reaction a direct or indirect anti-globulin test may be positive and the peripheral blood smear may show spherocytes
Management in an acute hemolytic transfusion reaction is mainly supportive.
Their should be prompt interruption of the transfusion, saving of the blood for testing, early blood in urine sampling, vigorous hydration with isotonic saline to maintain high urine output to minimize the free heme mediated renal vascular injury.
Manitol administration has not been evidence based.
Diuretics and forced alkaline diuresis may be helpful along with sodium bicarbonate infusion to achieve a urinary pH of more than 6.5.
Hyperkalemia, pressor support and management of DIC may be required.
No evidence supports the routine use of glucocorticoids, intravenous immunoglobulin, or plasma exchange.